EP0318393A1 - Use of ademetionine against ageing of the skin - Google Patents

Use of ademetionine against ageing of the skin Download PDF

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Publication number
EP0318393A1
EP0318393A1 EP88402968A EP88402968A EP0318393A1 EP 0318393 A1 EP0318393 A1 EP 0318393A1 EP 88402968 A EP88402968 A EP 88402968A EP 88402968 A EP88402968 A EP 88402968A EP 0318393 A1 EP0318393 A1 EP 0318393A1
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Prior art keywords
ademetionine
salt
salts
skin
weight
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EP88402968A
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German (de)
French (fr)
Inventor
Gérard Le Fur
Michèle Bousquet
Emilio Crisafulli
Michel Sabadie
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Elf Sanofi SA
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Sanofi SA
Elf Sanofi SA
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Publication of EP0318393A1 publication Critical patent/EP0318393A1/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • the present invention relates to the use of ademetionine and its salts for the preparation of cosmetic and pharmaceutical compositions opposing the aging of the skin and the cosmetic compositions thus obtained.
  • Ademetionine is the International Nonproprietary Name for the internal salt of (S) -5 ′ - [(3-amino-3-carboxypropyl) -methylsulfonio] -5′-deoxyadenosine hydroxide also called S-adenosyl-L-methionine or more simply SAM.
  • Ademetionine is a physiological molecule of almost ubiquitous distribution in the tissues and in the fluids of the organism where it intervenes in important biological processes as a donor of methyl groups in numerous transmethylation reactions and as a precursor of physiological sulfur compounds such as glutathione, cysteine, taurine, CoA.
  • Ademetionine is the active principle of medicinal products, in particular for the treatment of degenerative osteoarthropathies where it plays an important role through its antiphlogistic and analgesic activity due to its intervention in the metabolism of arachidonic acid and prostaglandins without interfering with platelet aggregation .
  • Ademetionine is also indicated for the treatment of depressive syndromes.
  • This active ingredient is neither toxic nor mutagenic and the medicines containing it do not have any side effects. troublesome.
  • These drugs are administered intramuscularly, intravenously or orally, although the possibility of administering them as topical anti-inflammatory drugs in liquids and ointments in which the active ingredient is diluted in ordinary solvents used in pharmacies has been provided (US 4,057,686) .
  • Ademetionine in the form of an internal salt is unstable and is preferably used, in pharmaceutical compositions, in the form of a salt with inorganic and / or organic acids such as carboxylic acids such as citrate, tartrate, malate or ascorbate (FR 2 275 220), strong mineral acids having a pK less than 2.5 (EP 73 376) and organic sulfonic acids having a pK less than 2.5 (EP 72 980, BE 831.310), sulfate p -toluenesulfonate or di-p-toluenesulfonate disulfate being the preferred salt.
  • Salts with polyanions have also been proposed (EP 191 133). To guarantee the good stability of ademetionine preparations, it is however desirable to mix the active ingredient with a stabilizer, for example, mannitol (EP 73 376), lactose or maltose (EP 108 817).
  • the present invention relates to the use of ademetionine and its salts for the preparation of pharmaceutical or cosmetic compositions intended to oppose the aging of the skin.
  • the action opposing aging is due to the biochemical properties of ademetionine.
  • Trans-methylation is verified on biological molecules, in particular skin proteins, nucleic acids and phospholipids, which are biotransformed and enter into anabolic and catabolic cycles.
  • This ana-catabolizing activity at the level of epidermal cells promotes their regeneration while the action on methyltransferases, by increasing the methylation of phospholipids, makes the cell membranes more fluid thus slowing down the natural aging process of the skin.
  • ademetionine can be used in the form of any of the salts indicated above, preferably the dihydrochloride, the disulfate, the salt with 2.5 molecules of sulfuric acid, p-toluenesulfonate, di-p-toluenesulfonate, tri-p-toluenesulfonate, disulfate di-p-toluene sulfonate or the salts with polyanions.
  • the salts with a cellulose sulphate such as the cellulose 6-sulphate described in EP 116 251, with a chitin sulphate such as the chitin 6-sulphate described in EP 116 251 or with a chitosan sulphate such than the chitosan 6-sulfate described in EP 148 057, are particularly preferred.
  • the ademetionine salts can be used as such or in the presence of stabilizing agents, for example mannitol, lactose, maltose and / or adjuvants such as a fatty acid.
  • stabilizing agents for example mannitol, lactose, maltose and / or adjuvants such as a fatty acid.
  • Mannitol is generally involved in the ratio: ademetionine or one of its salts / mannitol of approximately 3/1.
  • Ademetionine and its salts are used, for the preparation of the pharmaceutical or cosmetic compositions according to the invention, in amounts sufficient to produce the therapeutic or cosmetic effect, in particular at a concentration of 0.001 to 5% by weight, desirably at a concentration of 0.001 to 1% and preferably 0.05 to 0.2%.
  • the active ingredient is mixed with pharmaceutical or cosmetic excipients to prepare ointments, creams, lotions, emulsions or solutions.
  • the active ingredient can also be packaged for oral or parenteral administration, according to known methods.
  • the active principle is mixed with the excipients generally used in the pharmaceutical technique for compositions for topical use such as, for example, fats of animal origin, vegetable oils, saturated fatty acids. or unsaturated, alcohols, polyalkylene glycols, waxes, petrolatum, polyesters which can be combined with water and with gelling agents when they are compatible.
  • excipients generally used in the pharmaceutical technique for compositions for topical use
  • alcohols polyalkylene glycols
  • waxes waxes
  • petrolatum petrolatum
  • polyesters which can be combined with water and with gelling agents when they are compatible.
  • other ingredients compatible with ademetionine and its salts can be added such as antibacterial agents or perfumes.
  • Ademetionine in particular in the form of one of its salts, is preferably used for the preparation of cosmetic compositions intended to counter aging of the skin, more particularly intended for: - slow aging by maintaining optimum fluidity of the membranes of the skin cells, a high membrane fluidity promoting internal intercellular swelling therefore an optimum metabolism; - improve the condition of prematurely aged skin by the action of exogenous factors, according to the above process.
  • the ademetionine salt is used as such or in the form of an encapsulation complex, for example of the liposome or phytosome type, coating with a protective film or complexation with a protein system, to prepare cosmetics in the form of emulsions, aqueous or anhydrous gels, two-phase systems with extemporaneous mixing in which the ademetionine salt is in solid form, make-up products, lotions based on alcohol or not, optionally in the presence of a stabilizer.
  • the present invention therefore relates to cosmetic compositions based on ademetionine or one of its salts.
  • ademetionine is preferably used in the form of a salt, preferably one of the salts mentioned above, and, optionally, as a mixture with a stabilizing agent such as mannitol, lactose, maltose or a cyclodextrin, the preferred stabilizing agent being mannitol.
  • the preferred mixture is ademionion disulfate di-p-toluenesulfonate / mannitol in a ratio 2: 1 to 4: 1, preferably 3: 1.
  • the cosmetic compositions of the present invention can also contain adjuvants such as fatty acids, saturated or unsaturated, unsubstituted or substituted with a hydroxyl group, containing from 1 to 18 carbon atoms, or an alkaline salt of said fatty acids.
  • adjuvants such as fatty acids, saturated or unsaturated, unsubstituted or substituted with a hydroxyl group, containing from 1 to 18 carbon atoms, or an alkaline salt of said fatty acids.
  • the concentration can be from 0.001 to 5%; the desirable concentration is 0.001 to 1%, preferably 0.05 to 0.2% by weight.
  • the form of the cosmetic compositions according to the invention may be a cream in which ademetionine, one of its salts or a mixture of one of these products with the stabilizer is associated with the excipients commonly used in cosmetology, and compatible with the ademetionine and its salts, such as lanolin.
  • compositions of the invention can also be presented in the form of a gel in suitable excipients such as cellulose esters, fatty acid esters, for example isopropyl myristate or other gelling agents.
  • the cosmetic compositions according to the invention can also take the form of a lotion or solution in which the ademetionine, its salt or the mixture of one of these products with the stabilizer is dissolved or microdispersed in a microemulsion.
  • the form of the pharmaceutical or cosmetic compositions according to the invention can therefore be a microdispersion ademetionine in a liquid containing water, as well as one or more surfactants.
  • These dispersions have the characteristics of microemulsions and practically have the appearance of true solutions. They are preferably prepared immediately.
  • microemulsions have good stability and can be stored for the time necessary for use at temperatures between 0 and 60 ° C. without sedimentation of the constituents or phase separation.
  • the surfactants of the composition are chosen from surfactants which can be used in cosmetology.
  • surfactants which can be used in cosmetology.
  • a neutralizing agent can be added to the composition.
  • the optional neutralizing agent can consist either of a buffer mixture, for example a phosphate buffer, or simply of a biocompatible amine such as mono-, di- or tri-ethanolamine.
  • microemulsions are obtained which can be diluted in l in all proportions, regardless of the hydrometric degree of the water used.
  • HLB Lipophilic Hydrophilic Balance
  • compositions of the present invention are very well tolerated, they exhibit no phototoxicity and their application to the skin for extended periods of time does not imply any systemic effect. In general, after thirty days of application, there is an improvement in the appearance of the skin and a slowing down in the formation of wrinkles.
  • SAT ademetionine
  • SAM-2s ademetionine disulfate.
  • Aerosil 200 silica aerosol, marketed by DEGUSSA Solutol HS 15: Polyethylene glycol 600 12-hydroxystearate, marketed by BASF Labrafil 1944 CS: polyoxyethylenated unsaturated fatty acid triglycerides, marketed by GATTEFOSSE Acrysol: acylates / methacrylates copolymer, marketed by SEPPIC Finsolv TN: benzoates of alcohols containing 12-15 carbon atoms, marketed by WITCO Cetiol HE: polyethylene glycol-7 glyceryl cocoate, marketed by HENKEL Hydrophilic Labrafac: triglycerides containing 7-8 polyoxyethylenated carbon atoms, marketed by GATTEFOSSE Abil 8551 B: dimethicone copolyol, marketed by GOLDSCHMIDT Carbopol
  • microemulsion is prepared by mixing all of the excipients and stirring until a clear solution is obtained.
  • the SAM-2s, 2t component is added at the time of use and the microemulsion thus obtained remains stable for several days.
  • Microemulsion for extemporaneous preparation obtained as described in Example 2.
  • Microemulsion for extemporaneous preparation obtained as described in Example 2.
  • Microemulsion for extemporaneous preparation obtained as described in Example 2.
  • Microemulsion for extemporaneous preparation obtained as described in Example 2.
  • Microemulsion for extemporaneous preparation obtained as described in Example 2.
  • Microemulsion for extemporaneous preparation obtained as described in Example 2.
  • Microemulsion for extemporaneous preparation obtained as described in Example 2.
  • SAM-2s 2t 0.10% Solutol HS 15 1.00% Hydrophilic Labrafac 0.25% Cetiol HE 0.20% Abil 8551 B 0.05% Propylene glycol 12.50% Ethanol 12.50% Carbopol 934 0.40% Triethanolamine qs pH 6 Perfume qs Dye qs Water qs 100.0%
  • Fluid makeup base Ethoxylated soy sterols 4.00 g Soy sterols 0.50 g Glycerol monostearate 1.00 g Vegetable oil 1.50 g 2-ethylhexyl palmitate 4.00 g Ethyl alcohol 0.50 g Capric / caprylic triglycerides 1.50 g Silicone oil 1.00 g Mineral oil 1.80 g Lanolin alcohol 0.20 g Propylene glycol dipelargonate 3.00 g Lecithin 1.00 g Preservatives in butylene glycol: 5.00 g Phenoxyethanolamine 0.5 g Methyl 4-hydroxybenzoate 0.1 g Ethyl 4-hydroxybenzoate 0.1 g Propyl 4-hydroxybenzoate 0.1 g Butyl 4-hydroxybenzoate 0.1 g Butylene glycol 4.1 g Carbopol 0.20 g Triethanolamine 0.20 g Tetrasodium EDTA 0.10 g Alpha-tocopherol 0.01g Perfume

Abstract

The invention relates to the use of ademetionine or one of its salts for preparing pharmaceutical or cosmetic compositions intended for counteracting ageing of the skin. It also relates to the abovementioned cosmetic compositions.

Description

La présente invention concerne l'utilisation de l'adémétionine et de ses sels pour la préparation de compositions cosmétiques et pharmaceutiques s'opposant au vieillissement de la peau et les compositions cosmétiques ainsi obtenues.The present invention relates to the use of ademetionine and its salts for the preparation of cosmetic and pharmaceutical compositions opposing the aging of the skin and the cosmetic compositions thus obtained.

Adémétionine est la Dénomination Commune Internationale du sel interne de l'hydroxyde de (S)-5′-[(3-amino-3-carboxypropyl)-­méthylsulfonio]-5′-désoxyadénosine de formule

Figure imgb0001
appelé également S-adénosyl-L-méthionine ou plus simplement SAM.Ademetionine is the International Nonproprietary Name for the internal salt of (S) -5 ′ - [(3-amino-3-carboxypropyl) -methylsulfonio] -5′-deoxyadenosine hydroxide
Figure imgb0001
 also called S-adenosyl-L-methionine or more simply SAM.

L'adémétionine est une molécule physiologique de distribution quasi ubiquitaire dans les tissus et dans les liquides de l'organisme où elle intervient dans des processus biologiques importants comme donneur de groupes méthyle dans de nombreuses réactions de transméthylation et comme précurseur de composés soufrés physiologiques tels que le glutathion, la cystéine, la taurine, le CoA.Ademetionine is a physiological molecule of almost ubiquitous distribution in the tissues and in the fluids of the organism where it intervenes in important biological processes as a donor of methyl groups in numerous transmethylation reactions and as a precursor of physiological sulfur compounds such as glutathione, cysteine, taurine, CoA.

Il est connu que les taux d'adémétionine sont élevés chez l'enfant et l'adolescent alors qu'ils diminuent chez l'adulte et se réduisent ultérieurement à l'âge présénile et sénile.It is known that ademetionine levels are high in children and adolescents, while they decrease in adults and decrease later in the pre-senile and senile age.

L'adémétionine est le principe actif de médicaments notamment pour le traitement des ostéoarthropathies dégénératives où elle joue un rôle important par son activité antiphlogistique et analgésique due à son intervention dans le métabolisme de l'acide arachidonique et des prostaglandines sans interférer avec l'agrégation plaquettaire.Ademetionine is the active principle of medicinal products, in particular for the treatment of degenerative osteoarthropathies where it plays an important role through its antiphlogistic and analgesic activity due to its intervention in the metabolism of arachidonic acid and prostaglandins without interfering with platelet aggregation .

L'adémétionine est également indiquée dans le traitement des syndromes dépressifs.Ademetionine is also indicated for the treatment of depressive syndromes.

Ce principe actif n'est ni toxique, ni mutagène et les médicaments le contenant ne présentent pas d'effets secondaires gênants. Ces médicaments sont administrés par voie intramusculaire, intraveineuse ou orale, bien que la possibilité de les administrer comme anti-inflammatoires topiques dans des liquides et pommades dans lesquels le principe actif est dilué dans des solvants ordinaires utilisés en pharmacie ait été prévue (US 4,057,686).This active ingredient is neither toxic nor mutagenic and the medicines containing it do not have any side effects. troublesome. These drugs are administered intramuscularly, intravenously or orally, although the possibility of administering them as topical anti-inflammatory drugs in liquids and ointments in which the active ingredient is diluted in ordinary solvents used in pharmacies has been provided (US 4,057,686) .

L'adémétionine sous forme de sel interne est instable et est de préférence utilisée, dans les compositions pharmaceutiques, sous forme de sel avec des acides inorganiques et/ou organiques tels que les acides carboxyliques comme le citrate, le tartrate, le malate ou l'ascorbate (FR 2 275 220), les acides minéraux forts ayant un pK inférieur à 2,5 (EP 73 376) et les acides sulfoniques organiques ayant un pK inférieur à 2,5 (EP 72 980, BE 831,310), le sulfate p-toluènesulfonate ou le disulfate di-p-toluènesulfonate étant le sel préféré. Des sels avec des polyanions ont été également proposés (EP 191 133). Pour garantir la bonne stabilité des préparations à base d'adémétionine, il est cependant souhaitable de mélanger le principe actif avec un stabilisant, par exemple, du mannitol (EP 73 376), du lactose ou du maltose (EP 108 817).Ademetionine in the form of an internal salt is unstable and is preferably used, in pharmaceutical compositions, in the form of a salt with inorganic and / or organic acids such as carboxylic acids such as citrate, tartrate, malate or ascorbate (FR 2 275 220), strong mineral acids having a pK less than 2.5 (EP 73 376) and organic sulfonic acids having a pK less than 2.5 (EP 72 980, BE 831.310), sulfate p -toluenesulfonate or di-p-toluenesulfonate disulfate being the preferred salt. Salts with polyanions have also been proposed (EP 191 133). To guarantee the good stability of ademetionine preparations, it is however desirable to mix the active ingredient with a stabilizer, for example, mannitol (EP 73 376), lactose or maltose (EP 108 817).

On a maintenant trouvé que l'adémétionine a une action s'opposant au vieillissement de la peau.We have now found that ademetionine has an action opposing the aging of the skin.

Plus particulièrement, on a trouvé que l'adémétionine, dissoute ou dispersée dans un véhicule approprié, retarde le vieillissement de la peau en lui donnant également un aspect et une consistance agréables.More particularly, it has been found that ademetionine, dissolved or dispersed in an appropriate vehicle, delays aging of the skin by also giving it a pleasant appearance and consistency.

Ainsi, selon un de ses aspects, la présente invention concerne l'utilisation de l'adémétionine et de ses sels pour la préparation de compositions pharmaceutiques ou cosmétiques destinées à s'opposer au vieillissement de la peau.Thus, according to one of its aspects, the present invention relates to the use of ademetionine and its salts for the preparation of pharmaceutical or cosmetic compositions intended to oppose the aging of the skin.

L'action s'opposant au vieillissement est due aux propriétés biochimiques de l'adémétionine. La trans-méthylation se vérifie sur des molécules biologiques, notamment les protéines de la peau, les acides nucléiques et les phospholipides, qui sont biotransformées et entrent dans des cycles anaboliques et cataboliques. Cette activité ana-catabolisante au niveau des cellules épidermiques favorise leur régénération alors que l'action sur les méthyltransferases, par l'augmentation de la méthylation des phospholipides, rend plus fluides les membranes cellulaires ralentissant ainsi le processus naturel de vieillissement de la peau.The action opposing aging is due to the biochemical properties of ademetionine. Trans-methylation is verified on biological molecules, in particular skin proteins, nucleic acids and phospholipids, which are biotransformed and enter into anabolic and catabolic cycles. This ana-catabolizing activity at the level of epidermal cells promotes their regeneration while the action on methyltransferases, by increasing the methylation of phospholipids, makes the cell membranes more fluid thus slowing down the natural aging process of the skin.

Cette action fluidifiant les membranes a été mise en évidence sur des cellules de l'épiderme humain. La microviscosité de membrane des cellules épidermiques humaines a été étudiée selon la méthode de Shnitzkym et al. (J. Biol. Chem. 1974, 249, 2652-2657) en utilisant le diphénylhexatriène comme marqueur fluorescent. La présence d'adémétionine à une concentration molaire de 10⁻⁶ à 10⁻⁴ diminue la viscosité membranaire de 10 à 25 %.This fluidifying action on the membranes has been demonstrated on cells of the human epidermis. The membrane microviscosity of human epidermal cells was studied according to the method of Shnitzkym et al. (J. Biol. Chem. 1974, 249, 2652-2657) using diphenylhexatriene as a fluorescent marker. The presence of ademetionine at a molar concentration of 10⁻⁶ to 10⁻⁴ decreases the membrane viscosity by 10 to 25%.

Selon la présente invention, l'adémétionine peut être utilisée sous forme d'un quelconque des sels indiqués ci-dessus, de préférence le dichlorhydrate, le disulfate, le sel avec 2,5 molécules d'acide sulfurique, le p-toluènesulfonate, le di-p-toluènesulfonate, le tri-p-toluènesulfonate, le disulfate di-p-toluène sulfonate ou les sels avec les polyanions. Parmi ces derniers, les sels avec un sulfate de cellulose tel que le 6-sulfate de cellulose décrit dans EP 116 251, avec un sulfate de chitine tel que le 6-sulfate de chitine décrit dans EP 116 251 ou avec un sulfate de chitosane tel que le 6-sulfate de chitosane décrit dans EP 148 057, sont particulièrement préférés.According to the present invention, ademetionine can be used in the form of any of the salts indicated above, preferably the dihydrochloride, the disulfate, the salt with 2.5 molecules of sulfuric acid, p-toluenesulfonate, di-p-toluenesulfonate, tri-p-toluenesulfonate, disulfate di-p-toluene sulfonate or the salts with polyanions. Among the latter, the salts with a cellulose sulphate such as the cellulose 6-sulphate described in EP 116 251, with a chitin sulphate such as the chitin 6-sulphate described in EP 116 251 or with a chitosan sulphate such than the chitosan 6-sulfate described in EP 148 057, are particularly preferred.

Les sels d'adémétionine peuvent être utilisés tels quels ou en présence d'agents stabilisants, par exemple de mannitol, de lactose, de maltose et/ou d'adjuvants comme un acide gras.The ademetionine salts can be used as such or in the presence of stabilizing agents, for example mannitol, lactose, maltose and / or adjuvants such as a fatty acid.

Le mannitol intervient généralement dans le rapport : adémétionine ou un de ses sels/mannitol d'environ 3/1.Mannitol is generally involved in the ratio: ademetionine or one of its salts / mannitol of approximately 3/1.

L'adémétionine et ses sels sont utilisés, pour la préparation des compositions pharmaceutiques ou cosmétiques selon l'invention, dans des quantités suffisant à produire l'effet thérapeutique ou cosmétique, notamment à une concentration de 0,001 à 5 % en poids, de façon souhaitable à une concentration de 0,001 à 1 % et de préférence de 0,05 à 0,2 %.Ademetionine and its salts are used, for the preparation of the pharmaceutical or cosmetic compositions according to the invention, in amounts sufficient to produce the therapeutic or cosmetic effect, in particular at a concentration of 0.001 to 5% by weight, desirably at a concentration of 0.001 to 1% and preferably 0.05 to 0.2%.

Le principe actif est mélangé avec des excipients pharmaceutiques ou cosmétiques pour préparer des onguents, des crèmes, des lotions, des émulsions ou des solutions.The active ingredient is mixed with pharmaceutical or cosmetic excipients to prepare ointments, creams, lotions, emulsions or solutions.

Le principe actif peut également être conditionné pour des administrations par voie orale ou parentérale, selon des procédés connus.The active ingredient can also be packaged for oral or parenteral administration, according to known methods.

Pour préparer des compositions pharmaceutiques à usage local, le principe actif est mélangé aux excipients généralement employés dans la technique pharmaceutique pour les compositions à usage topique tels que, par exemple, les matières grasses d'origine animale, les huiles végétales, les acides gras saturés ou insaturés, les alcools, les glycols polyalkyléniques, les cires, la vaseline, les polyesters qui peuvent être associés à l'eau et àdes agents gélifiants lorsqu'ils sont compatibles. Dans ces préparations, on peut ajouter d'autres ingrédients compatibles avec l'adémétionine et ses sels comme des agents antibactériens ou des parfums.To prepare pharmaceutical compositions for local use, the active principle is mixed with the excipients generally used in the pharmaceutical technique for compositions for topical use such as, for example, fats of animal origin, vegetable oils, saturated fatty acids. or unsaturated, alcohols, polyalkylene glycols, waxes, petrolatum, polyesters which can be combined with water and with gelling agents when they are compatible. In these preparations, other ingredients compatible with ademetionine and its salts can be added such as antibacterial agents or perfumes.

L'adémétionine, notamment sous forme d'un de ses sels, est de préférence utilisée pour la préparation de compositions cosmétiques destinées à s'opposer au vieillissement de la peau, plus particulièrement destinées à :
- ralentir le vieillissement en maintenant une fluidité optimum des membranes des cellules cutanées, une fluidité membranaire élevée favorisant des écnahges intercellulaires internes donc un métabolisme optimum ;
- améliorer l'état des peaux vieillies prématurément par l'action de facteurs exogènes, selon le processus ci-dessus.Ademetionine, in particular in the form of one of its salts, is preferably used for the preparation of cosmetic compositions intended to counter aging of the skin, more particularly intended for:
- slow aging by maintaining optimum fluidity of the membranes of the skin cells, a high membrane fluidity promoting internal intercellular swelling therefore an optimum metabolism;
- improve the condition of prematurely aged skin by the action of exogenous factors, according to the above process.

Le sel d'adémétionine est utilisé tel quel ou sous forme de complexe d'encapsulation par exemple du type liposomes, phytosomes, enrobage par une pellicule protectrice ou complexation avec un système protéinique, pour préparer des cosmétiques se présentant sous la forme d'émulsions, de gels aqueux ou anhydres, de systèmes biphasiques à mélange extemporané dans lesquels le sel d'adémétionine est sous forme solide, de produits de maquillage, de lotions à base d'alcool ou non, éventuellement en présence d'un stabilisant.The ademetionine salt is used as such or in the form of an encapsulation complex, for example of the liposome or phytosome type, coating with a protective film or complexation with a protein system, to prepare cosmetics in the form of emulsions, aqueous or anhydrous gels, two-phase systems with extemporaneous mixing in which the ademetionine salt is in solid form, make-up products, lotions based on alcohol or not, optionally in the presence of a stabilizer.

Selon un autre de ses aspects, la présente invention concerne donc des compositions cosmétiques à base d'adémétionine ou d'un de ses sels. Dans ces compositions, l'adémétionine est de préférence utilisée sous forme de sel, de préférence d'un des sels cités ci-dessus, et, éventuellement, en mélange avec un agent stabilisant tel que le mannitol, le lactose, le maltose ou une cyclodextrine, l'agent stabilisant préféré étant le mannitol.According to another of its aspects, the present invention therefore relates to cosmetic compositions based on ademetionine or one of its salts. In these compositions, ademetionine is preferably used in the form of a salt, preferably one of the salts mentioned above, and, optionally, as a mixture with a stabilizing agent such as mannitol, lactose, maltose or a cyclodextrin, the preferred stabilizing agent being mannitol.

Lorsqu'on utilise un mélange sel d'adémétionine / stabilisant, le mélange préféré est adémétionine disulfate di-p-­toluènesulfonate/mannitol dans un rapport 2:1 à 4:1, de préférence 3:1.When using an ademetionine salt / stabilizer mixture, the preferred mixture is ademionion disulfate di-p-toluenesulfonate / mannitol in a ratio 2: 1 to 4: 1, preferably 3: 1.

Les compositions cosmétiques de la présente invention peuvent également contenir des adjuvants tels que des acides gras, saturés ou insaturés, non substitués ou substitués avec un groupe hydroxyle, contenant de 1 à 18 atomes de carbone, ou un sel alcalin desdits acides gras.The cosmetic compositions of the present invention can also contain adjuvants such as fatty acids, saturated or unsaturated, unsubstituted or substituted with a hydroxyl group, containing from 1 to 18 carbon atoms, or an alkaline salt of said fatty acids.

Dans ces compositions, la concentration peut être de 0,001 à 5 % ; la concentration souhaitable est de 0,001 à 1 %, de préférence de 0.05 à 0,2 % en poids.In these compositions, the concentration can be from 0.001 to 5%; the desirable concentration is 0.001 to 1%, preferably 0.05 to 0.2% by weight.

La forme des compositions cosmétiques selon l'invention peut être une crème dans laquelle l'adémétionine, un de ses sels ou un mélange d'un de ces produits avec le stabilisant est associé aux excipients couramment utilisés dans la cosmétologie, et compatibles avec l'adémétionin et ses sels, tels que la lanoline.The form of the cosmetic compositions according to the invention may be a cream in which ademetionine, one of its salts or a mixture of one of these products with the stabilizer is associated with the excipients commonly used in cosmetology, and compatible with the ademetionine and its salts, such as lanolin.

Les compositions cosmétiques de l'invention peuvent être également présentées sous forme de gel dans les excipients appropriés tels que les esters de cellulose, les esters d'acides gras, par exemple le myristate d'isopropyle ou d'autres agents gélifiants.The cosmetic compositions of the invention can also be presented in the form of a gel in suitable excipients such as cellulose esters, fatty acid esters, for example isopropyl myristate or other gelling agents.

Les compositions cosmétiques suivant l'invention peuvent aussi prendre la forme de lotion ou solution dans laquelle l'adémétionine, son sel ou le mélange d'un de ces produits avec le stabilisant est dissout ou microdispersé dans une microémulsion.The cosmetic compositions according to the invention can also take the form of a lotion or solution in which the ademetionine, its salt or the mixture of one of these products with the stabilizer is dissolved or microdispersed in a microemulsion.

La forme des compositions pharmaceutiques ou cosmétiques suivant l'invention peut donc être une microdispersion d'adémétionine dans un liquide contenant de l'eau, ainsi qu'un ou plusieurs agents tensioactifs. Ces dispersions présentent les caractères des microémulsions et ont pratiquement l'aspect de solutions vraies. Elles sont de préférence préparées extemporanément.The form of the pharmaceutical or cosmetic compositions according to the invention can therefore be a microdispersion ademetionine in a liquid containing water, as well as one or more surfactants. These dispersions have the characteristics of microemulsions and practically have the appearance of true solutions. They are preferably prepared immediately.

Ces microémulsions jouissent d'une bonne stabilité et peuvent être conservées pendant le temps nécessaire pour l'utilisation à des températures comprises entre 0 et 60° C sans qu'il y ait sédimentation des constituants ou séparation de phases.These microemulsions have good stability and can be stored for the time necessary for use at temperatures between 0 and 60 ° C. without sedimentation of the constituents or phase separation.

Les tensioactifs de la composition sont choisis parmi les agents de surface utilisables en cosmétologie. On peut indiquer à titre d'exemples non limitatifs : esters de sorbitol et leurs dérivés polyoxyéthylénés, les huiles de ricin (hydrogénées ou non) polyoxyéthylénées, les copolymères séquencés oxyde d'éthylène/oxyde de propylène, les alcools gras polyoxyéthylénés, le laurylsulfate de sodium, le dioctylsulfosuccinate de sodium, les lécithines d'oeuf ou de soja.The surfactants of the composition are chosen from surfactants which can be used in cosmetology. As nonlimiting examples, it is possible to indicate: sorbitol esters and their polyoxyethylenated derivatives, castor oils (hydrogenated or not) polyoxyethylenated, ethylene oxide / propylene oxide block copolymers, polyoxyethylenated fatty alcohols, lauryl sulphate sodium, sodium dioctylsulfosuccinate, egg or soy lecithins.

Lorsque l'adémétionine est utilisée sous forme de sel, si l'on souhaite maintenir le pH voisin de la neutralité, on peut ajouter à la composition un agent de neutralisation. L'agent neutralisant éventuel peut être constitué soit par un mélange tampon par exemple un tampon phosphate, soit simplement par une amine biocompatible telle que la mono-, la di- ou la tri-éthanolamine.When ademetionine is used in the form of a salt, if it is desired to maintain the pH close to neutrality, a neutralizing agent can be added to the composition. The optional neutralizing agent can consist either of a buffer mixture, for example a phosphate buffer, or simply of a biocompatible amine such as mono-, di- or tri-ethanolamine.

Selon un mode de réalisation préférée, en utilisant des agents tensioactifs dont la Balance Hydrophile Lipophile (HLB) est comprise entre 10 et 17 et de préférence entre 11 et 15, dans un pourcentage de 7 à 40 %, on obtient des microémulsions diluables dans l'eau en toutes proportions et ce, quel que soit le degré hydrométrique de l'eau utilisée.According to a preferred embodiment, using surfactants whose Lipophilic Hydrophilic Balance (HLB) is between 10 and 17 and preferably between 11 and 15, in a percentage of 7 to 40%, microemulsions are obtained which can be diluted in l in all proportions, regardless of the hydrometric degree of the water used.

De telles dilutions restent stables pendant plusieurs jours, ce qui est très suffisant compte tenu de leur utilisation.Such dilutions remain stable for several days, which is very sufficient in view of their use.

Les compositions pharmaceutiques ou cosmétiques de la présente invention sont très bien tolérées, elles ne présentent aucune phototoxicité et leur application sur la peau pour des périodes de temps prolongées n'implique aucun effet systémique. En général, après trente jours d'application, on note une amélioration de l'aspect de la peau et un ralentissement dans la formation des rides.The pharmaceutical or cosmetic compositions of the present invention are very well tolerated, they exhibit no phototoxicity and their application to the skin for extended periods of time does not imply any systemic effect. In general, after thirty days of application, there is an improvement in the appearance of the skin and a slowing down in the formation of wrinkles.

Les exemples suivants illustrent l'invention sans toutefois la limiter. Dans ces exemples, on utilisera les abréviations suivantes : SAM = adémétionine, SAM-2s,2t = adémétionine disulfate, di-p-toluènesulfonate, SAM-2s = adémétionine disulfate. The following examples illustrate the invention without, however, limiting it. In these examples, the following abbreviations will be used: SAT = ademetionine, SAM-2s, 2t = ademetionine disulfate, di-p-toluenesulfonate, SAM-2s = ademetionine disulfate.

Dans un souci de simplification, certains constituants des compositions ont été désignés par leur dénomination commerciale dont voici les significations : Aerosil 200 : aérosol de silice, commercialisé par DEGUSSA Solutol HS 15 : 12-hydroxystéarate de polyéthylèneglycol 600, commercialisé par BASF Labrafil 1944 CS : triglycérides d'acides gras insaturés polyoxyéthylénés, commercialisé par GATTEFOSSE Acrysol : copolymère acylates/méthacrylates, commercialisé par SEPPIC Finsolv TN : benzoates d'alcools contenant 12-15 atomes de carbone, commercialisé par WITCO Cetiol HE : polyéthylèneglycol-7 glycéryl cocoate, commercialisé par HENKEL Labrafac hydrophile : triglycérides contenant 7-8 atomes de carbone polyoxyéthylénés, commercialisé par GATTEFOSSE Abil 8551 B : diméthicone copolyol, commercialisé par GOLDSCHMIDT Carbopol 934 : carboxypolyméthylène, commercialisé par GOLDSCHMIDT Carbopol 940 : carboxypolyméthylène, commercialisé par GOLDSCHMIDT EDTA : acide éthylènediaminotétracétique Filtre UVA-UVB : 4-méthoxycinnamate d'éthyle-2 hexyle (marque PARFOL MCX). For the sake of simplification, certain constituents of the compositions have been designated by their commercial name, the meanings of which are as follows: Aerosil 200: silica aerosol, marketed by DEGUSSA Solutol HS 15: Polyethylene glycol 600 12-hydroxystearate, marketed by BASF Labrafil 1944 CS: polyoxyethylenated unsaturated fatty acid triglycerides, marketed by GATTEFOSSE Acrysol: acylates / methacrylates copolymer, marketed by SEPPIC Finsolv TN: benzoates of alcohols containing 12-15 carbon atoms, marketed by WITCO Cetiol HE: polyethylene glycol-7 glyceryl cocoate, marketed by HENKEL Hydrophilic Labrafac: triglycerides containing 7-8 polyoxyethylenated carbon atoms, marketed by GATTEFOSSE Abil 8551 B: dimethicone copolyol, marketed by GOLDSCHMIDT Carbopol 934: carboxypolymethylene, marketed by GOLDSCHMIDT Carbopol 940: carboxypolymethylene, marketed by GOLDSCHMIDT EDTA: ethylenediaminotetracetic acid UVA-UVB filter: 2-ethyl hexyl-4-methoxycinnamate (brand PARFOL MCX).

EXEMPLE 1EXAMPLE 1

Gel à base d'un mélange de SAM disulfate, ditosilate/mannitol 3/1, à 1 % de SAM base SAM-2s,2t 2,88 g Aerosil 200 7,00 g Myristate d'isopropyle à 100,00 g Gel based on a mixture of SAM disulfate, ditosilate / mannitol 3/1, with 1% of SAM base SAM-2s, 2t 2.88 g Aerosil 200 7.00 g Isopropyl myristate at 100.00 g

EXEMPLE 2EXAMPLE 2

Microémulsion pour préparation extemporanée SAM-2s,2t 0,1 % Solutol HS 15 2,0 % Labrafil 1944 CS 1,0 % Eau q.s.p. 100,0 % Microemulsion for extemporaneous preparation SAM-2s, 2t 0.1% Solutol HS 15 2.0% Labrafil 1944 CS 1.0% Water qs 100.0%

La microémulsion est préparée en mélangeant l'ensemble des excipients et agitant jusqu'à l'obtention d'une solution limpide.The microemulsion is prepared by mixing all of the excipients and stirring until a clear solution is obtained.

Le composant SAM-2s,2t est ajouté au moment de l'utilisation et la microémulsion ainsi obtenue reste stable plusieurs jours.The SAM-2s, 2t component is added at the time of use and the microemulsion thus obtained remains stable for several days.

EXEMPLE 3EXAMPLE 3

Microémulsion pour préparation extemporanée obtenue comme décrit dans l'exemple 2. SAM-2s,2t 0,1 % Solutol HS 15 4,0 % Labrafil 1944 CS 2,0 % Eau q.s.p. 100,0 % Microemulsion for extemporaneous preparation obtained as described in Example 2. SAM-2s, 2t 0.1% Solutol HS 15 4.0% Labrafil 1944 CS 2.0% Water qs 100.0%

EXEMPLE 4EXAMPLE 4

Microémulsion pour préparation extemporanée obtenue comme décrit dans l'exemple 2. SAM-2s,2t 0,1 % Finsolv TN 5,5 % Solutol HS 15 8,0 % Eau q.s.p. 100,0 % Microemulsion for extemporaneous preparation obtained as described in Example 2. SAM-2s, 2t 0.1% Finsolv TN 5.5% Solutol HS 15 8.0% Water qs 100.0%

EXEMPLE 5EXAMPLE 5

Microémulsion pour préparation extemporanée obtenue comme décrit dans l'exemple 2. SAM-2s,2t 0,1 % Solutol HS 15 4,0 % Labrafil 1944 CS 2,0 % Hydroxyéthyl cellulose 0,5 % Eau q.s.p. 100,0 % Microemulsion for extemporaneous preparation obtained as described in Example 2. SAM-2s, 2t 0.1% Solutol HS 15 4.0% Labrafil 1944 CS 2.0% Hydroxyethyl cellulose 0.5% Water qs 100.0%

EXEMPLE 6EXAMPLE 6

Microémulsion pour préparation extemporanée obtenue comme décrit dans l'exemple 2. SAM-2s,2t 0,1 % Solutol HS 15 4,0 % Labrafil 1944 CS 2,0 % Hydroxyéthyl cellulose 1,0 % Eau q.s.p. 100,0 % Microemulsion for extemporaneous preparation obtained as described in Example 2. SAM-2s, 2t 0.1% Solutol HS 15 4.0% Labrafil 1944 CS 2.0% Hydroxyethyl cellulose 1.0% Water qs 100.0%

EXEMPLE 7EXAMPLE 7

Microémulsion pour préparation extemporanée obtenue comme décrit dans l'exemple 2. SAM-2s,2t 0,1 % Solutol HS 15 4,0 % Labrafil 1944 CS 2,0 % Acrysol 1,0 % Eau q.s.p. 100,0 % Microemulsion for extemporaneous preparation obtained as described in Example 2. SAM-2s, 2t 0.1% Solutol HS 15 4.0% Labrafil 1944 CS 2.0% Acrysol 1.0% Water qs 100.0%

EXEMPLE 8EXAMPLE 8

Microémulsion pour préparation extemporanée obtenue comme décrit dans l'exemple 2. SAM-2s,2t 0,1 % Solutol HS 15 4,0 % Labrafil 1944 CS 2,0 % Acrysol 2,0 % Eau q.s.p. 100,0 % Microemulsion for extemporaneous preparation obtained as described in Example 2. SAM-2s, 2t 0.1% Solutol HS 15 4.0% Labrafil 1944 CS 2.0% Acrysol 2.0% Water qs 100.0%

EXEMPLE 9EXAMPLE 9

Microémulsion pour préparation extemporanée obtenue comme décrit dans l'exemple 2. SAM-2s,2t 0,10 % Solutol HS 15 1,00 % Labrafac Hydrophile 0,25 % Cetiol HE 0,20 % Abil 8551 B 0,05 % Propylèneglycol 12,50 % Ethanol 12,50 % Carbopol 934 0,40 % Triéthanolamine q.s.p. pH 6 Parfum q.s. Colorant q.s. Eau q.s.p. 100,0 % Microemulsion for extemporaneous preparation obtained as described in Example 2. SAM-2s, 2t 0.10% Solutol HS 15 1.00% Hydrophilic Labrafac 0.25% Cetiol HE 0.20% Abil 8551 B 0.05% Propylene glycol 12.50% Ethanol 12.50% Carbopol 934 0.40% Triethanolamine qs pH 6 Perfume qs Dye qs Water qs 100.0%

EXEMPLE 10EXAMPLE 10

Préparation extemporanée
A/ Solvant: Carboxyméthylcellulose 0,30 g Conservateurs dans propylène glycol : 5,00 g     Phénoxyéthanol    0,5 g     4-hydroxybenzoate de méthyle    0,1 g     4-hydroxybenzoate d'éthyle    0,1 g     4-hydroxybenzoate de propyle    0,1 g     4-hydroxybenzoate de butyle    0,1 g     Propylène glycol    4,1 g Huile de ricin hydrogénée éthoxylée 1,00 g Parfum 0,20 g Eau déminéralisée q.s.p. 100,00 g B/ Poudre : SAM-2s 0,01 g Lactose q.s.p. 100,00 g Extemporaneous preparation
A / Solvent: Carboxymethylcellulose 0.30 g Preservatives in propylene glycol: 5.00 g Phenoxyethanol 0.5 g Methyl 4-hydroxybenzoate 0.1 g Ethyl 4-hydroxybenzoate 0.1 g Propyl 4-hydroxybenzoate 0.1 g Butyl 4-hydroxybenzoate 0.1 g Propylene glycol 4.1 g Ethoxylated hydrogenated castor oil 1.00 g Perfume 0.20 g Demineralized water qs 100.00 g B / Powder: SAM-2s 0.01g Lactose qs 100.00 g

EXEMPLE 11EXAMPLE 11

Crème de nuit Alcool cétylique 2,00 g Stéarine 2,50 g Monostéarate de glycérol 5,00 g Palmitate d'isopropyle 5,00 g Huile végétale 3,00 g Huile minérale 2,00 g Perhydrosqualène 2,00 g Huile de solicone 1,00 g Beurre de karité 2,00 g Palmitate d'éthyle-2 hexyle 5,00 g Triéthanolamine 5,50 g Conservateurs dans butylène glycol : 5,00 g     Phénoxyéthanol    0,5 g     4-hydroxybenzoate de méthyle    0,1 g     4-hydroxybenzoate d'éthyle    0,1 g     4-hydroxybenzoate de propyle    0,1 g     4-hydroxybenzoate de butyle    0,1 g     Butylène glycol    4,1 g EDTA tétrasodique 0,10 g Parfum 0,30 g SAM-2s 0,01 g Eau q.s.p. 100,00 g Night cream Cetyl alcohol 2.00 g Stearine 2.50 g Glycerol monostearate 5.00 g Isopropyl palmitate 5.00 g Vegetable oil 3.00 g Mineral oil 2.00 g Perhydrosqualene 2.00 g Solicone oil 1.00 g Shea Butter 2.00 g 2-ethylhexyl palmitate 5.00 g Triethanolamine 5.50 g Preservatives in butylene glycol: 5.00 g Phenoxyethanol 0.5 g Methyl 4-hydroxybenzoate 0.1 g Ethyl 4-hydroxybenzoate 0.1 g Propyl 4-hydroxybenzoate 0.1 g Butyl 4-hydroxybenzoate 0.1 g Butylene glycol 4.1 g Tetrasodium EDTA 0.10 g Perfume 0.30 g SAM-2s 0.01g Water qs 100.00 g

EXEMPLE 12EXAMPLE 12

Crème de jour protectrice Monostéarate de sorbitan éthoxylé 2,60 g Huile de silicone 1,00 g Alcool cétylique 2,00 g Huile minérale 3,00 g Alcool de lanoline 1,00 g Perhydrosqualène 1,00 g Monostéarate de sorbitan 2,40 g Palmitate de cétyle 3,00 g Palmitate d'isopropyle 4,00 g Filtre UVA-UVB 2,00 g EDTA tétrasodique 0,10 g Carbopol 0,30 g Triéthanolamine 0,30 g Alpha-tocophérol 0,01 g Conservateurs dans butylène glycol : 5,00 g     Phénoxyéthanol    0,5 g     4-hydroxybenzoate de méthyle    0,1 g     4-hydroxybenzoate d'éthyle    0,1 g     4-hydroxybenzoate de propyle    0,1 g     4-hydroxybenzoate de butyle    0,1 g     Butylène glycol    4,1 g Parfum 0,30 g SAM-2s 0,01 g Eau déminéralisée q.s.p. 100,00 g Protective day cream Ethoxylated sorbitan monostearate 2.60 g Silicone oil 1.00 g Cetyl alcohol 2.00 g Mineral oil 3.00 g Lanolin alcohol 1.00 g Perhydrosqualene 1.00 g Sorbitan monostearate 2.40 g Cetyl palmitate 3.00 g Isopropyl palmitate 4.00 g UVA-UVB filter 2.00 g Tetrasodium EDTA 0.10 g Carbopol 0.30 g Triethanolamine 0.30 g Alpha-tocopherol 0.01g Preservatives in butylene glycol: 5.00 g Phenoxyethanol 0.5 g Methyl 4-hydroxybenzoate 0.1 g Ethyl 4-hydroxybenzoate 0.1 g Propyl 4-hydroxybenzoate 0.1 g Butyl 4-hydroxybenzoate 0.1 g Butylene glycol 4.1 g Perfume 0.30 g SAM-2s 0.01g Demineralized water qs 100.00 g

EXEMPLE 13EXAMPLE 13

Gel Carbopol 940 0,20 g Polyéthylène glycol 3,00 g Alpha-tocophérol 0,01 g Conservateurs dans butylène glycol : 5,00 g     Phénoxyéthanol    0,5 g     4-hydroxybenzoate de méthyle    0,1 g     4-hydroxybenzoate d'éthyle    0,1 g     4-hydroxybenzoate de propyle    0,1 g     4-hydroxybenzoate de butyle     0,1 g     Butylène glycol    4,1 g Parfum 0,30 g Triéthanolamine 0,25 g SAM-2s 0,01 g Eau déminéralisée q.s.p. 100,00 Gel Carbopol 940 0.20 g Polyethylene glycol 3.00 g Alpha-tocopherol 0.01g Preservatives in butylene glycol: 5.00 g Phenoxyethanol 0.5 g Methyl 4-hydroxybenzoate 0.1 g Ethyl 4-hydroxybenzoate 0.1 g Propyl 4-hydroxybenzoate 0.1 g Butyl 4-hydroxybenzoate 0.1 g Butylene glycol 4.1 g Perfume 0.30 g Triethanolamine 0.25 g SAM-2s 0.01g Demineralized water qs 100.00

EXEMPLE 14EXAMPLE 14

Base fluide de maquillage Stérols de soja éthoxylés 4,00 g Stérols de soja 0,50 g Monostéarate de glycérol 1,00 g Huile végétale 1,50 g Palmitate d'éthyle-2 hexyle 4,00 g Alcool céthylique 0,50 g Triglycérides capriques/capryliques 1,50 g Huile de silicone 1,00 g Huile minérale 1,80 g Alcool de lanoline 0,20 g Dipélargonate de propylène glycol 3,00 g Lécithine 1,00 g Conservateurs dans butylène glycol : 5,00 g     Phénoxyéthanolamine    0,5 g     4-hydroxybenzoate de méthyle    0,1 g     4-hydroxybenzoate d'éthyle    0,1 g     4-hydroxybenzoate de propyle    0,1 g     4-hydroxybenzoate de butyle    0,1 g     Butylène glycol    4,1 g Carbopol 0,20 g Triéthanolamine 0,20 g EDTA tétrasodique 0,10 g Alpha-tocophérol 0,01 g Parfum 0,30 g SAM-2s 0,01 g Eau déminéralisée q.s.p. 100,00 g Fluid makeup base Ethoxylated soy sterols 4.00 g Soy sterols 0.50 g Glycerol monostearate 1.00 g Vegetable oil 1.50 g 2-ethylhexyl palmitate 4.00 g Ethyl alcohol 0.50 g Capric / caprylic triglycerides 1.50 g Silicone oil 1.00 g Mineral oil 1.80 g Lanolin alcohol 0.20 g Propylene glycol dipelargonate 3.00 g Lecithin 1.00 g Preservatives in butylene glycol: 5.00 g Phenoxyethanolamine 0.5 g Methyl 4-hydroxybenzoate 0.1 g Ethyl 4-hydroxybenzoate 0.1 g Propyl 4-hydroxybenzoate 0.1 g Butyl 4-hydroxybenzoate 0.1 g Butylene glycol 4.1 g Carbopol 0.20 g Triethanolamine 0.20 g Tetrasodium EDTA 0.10 g Alpha-tocopherol 0.01g Perfume 0.30 g SAM-2s 0.01g Demineralized water qs 100.00 g

Claims (14)

1. Utilisation de l'adémétionine ou d'un de ses sels pour la préparation de compositions pharmaceutiques ou cosmétiques destinées à s'opposer au vieillissement de la peau.1. Use of ademetionine or one of its salts for the preparation of pharmaceutical or cosmetic compositions intended to counter aging of the skin. 2. Utilisation selon la revendication 1, caractérisée en ce que le sel d'adémétionine est le disulfate di-p-toluènesulfonate ou le disulfate.2. Use according to claim 1, characterized in that the ademetionine salt is di-p-toluenesulfonate disulfate or disulfate. 3. Utilisation selon la revendication 1, caractérisée en ce que le sel d'adémétionine est un sel avec un polyanion.3. Use according to claim 1, characterized in that the ademetionine salt is a salt with a polyanion. 4. Utilisation selon la revendication 3, caractérisée en ce que le polyanion est un sulfate de cellulose, un sulfate de chitine ou le chitosane 6-sulfate.4. Use according to claim 3, characterized in that the polyanion is a cellulose sulphate, a chitin sulphate or the chitosan 6-sulphate. 5. Utilisation selon l'une quelconque des revendications 1 à 4, caractérisée en ce que l'adémétionine ou son sel est mélangée à un agent stabilisant tel que le mannitol, le lactose ou le maltose.5. Use according to any one of claims 1 to 4, characterized in that ademetionine or its salt is mixed with a stabilizing agent such as mannitol, lactose or maltose. 6. Utilisation selon la revendication 5, caractérisée en ce que le rapport adémétionine, ou sel d'adémétionine/mannitol est environ 3/1.6. Use according to claim 5, characterized in that the ademetionine, or ademetionine / mannitol salt ratio is approximately 3/1. 7. Utilisation selon l'une quelconque des revendications 1 à 6 pour la préparation extemporanée de compositions pharmaceutiques ou cosmétiques destinées à s'opposer au vieillissement de la peau, sous forme de microémulsions.7. Use according to any one of claims 1 to 6 for the extemporaneous preparation of pharmaceutical or cosmetic compositions intended to oppose the aging of the skin, in the form of microemulsions. 8. Utilisation selon l'une quelconque des revendications précédentes, pour la préparation de compositions contenant de 0,001 à 5 % en poids, généralement de 0,001 à 1 % en poids et de préférence de 0,05 à 0,2 % en poids d'adémétionine ou d'un de ses sels.8. Use according to any one of the preceding claims, for the preparation of compositions containing from 0.001 to 5% by weight, generally from 0.001 to 1% by weight and preferably from 0.05 to 0.2% by weight of ademetionine or one of its salts. 9. Composition cosmétique caractérisée en ce qu'elle renferme de l'adémétionine ou l'un de ses sels.9. Cosmetic composition characterized in that it contains ademetionine or one of its salts. 10. Composition cosmétique selon la revendication 9, caractérisée en ce qu'elle renferme en outre un agent stabilisant.10. Cosmetic composition according to claim 9, characterized in that it also contains a stabilizing agent. 11. Composition cosmétique selon la revendication 10, caractérisée en ce qu'elle renferme un mélange adémétionine disulfate di-p-toluènesulfonate/mannitol dans un rapport 3/1 environ.11. Cosmetic composition according to claim 10, characterized in that it contains an ademetionine mixture di-p-toluenesulfonate / mannitol disulfate in a 3/1 ratio approximately. 12. Composition selon l'une des revendications 9 ou 10, caractérisée en ce qu'elle renferme l'adémétionine disulfate.12. Composition according to one of claims 9 or 10, characterized in that it contains ademetionine disulfate. 13. Composition selon l'une quelconque des revendications 9 à 12, caractérisée en ce qu'elle contient l'adémétionine ou son sel à une concentration de 0,001 à 5 % en poids dans un excipient cosmétique.13. Composition according to any one of claims 9 to 12, characterized in that it contains ademetionine or its salt at a concentration of 0.001 to 5% by weight in a cosmetic excipient. 14. Composition selon la revendication 13, caractérisée en ce qu'elle contient l'adémétionine ou son sel à une concentration de 0,001 à 1 % en poids, de préférence 0,05 à 0,2 % en poids.14. Composition according to claim 13, characterized in that it contains ademetionine or its salt at a concentration of 0.001 to 1% by weight, preferably 0.05 to 0.2% by weight.
EP88402968A 1987-11-25 1988-11-25 Use of ademetionine against ageing of the skin Withdrawn EP0318393A1 (en)

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FR8716349A FR2623396B1 (en) 1987-11-25 1987-11-25 USE OF ADEMETIONINE AGAINST AGING SKIN
FR8716349 1987-11-25

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FR3029418A1 (en) * 2014-12-09 2016-06-10 Michel Frey COMPOSITION FOR SLOWING THE SIGNS OF PATHOLOGICAL OR PHYSIOLOGICAL AGING.
WO2016092193A1 (en) * 2014-12-09 2016-06-16 Michel Frey Composition for slowing cellular ageing, associated food supplement

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US4956173A (en) 1990-09-11
PT89076B (en) 1993-04-30
FR2623396A1 (en) 1989-05-26
JPH01193206A (en) 1989-08-03
FR2623396B1 (en) 1990-03-30
PT89076A (en) 1988-12-01

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